This proposal, submitted by an early stage investigator, seeks four years of R01 support to conduct an MRI study of adolescent patients with serious substance and conduct problems and adolescent controls. This proposal seeks to identify the neural correlates (both functional and structural) of callous-unemotionality (CU). CU is identifiable in childhood and adolescence, is a relatively stable trait into adulthood, and is linked with persistent antisocial behavior problems and substance dependence; individuals with CU, antisocial behavior problems and substance use disorders appear more resistant to treatment. This proposal will also allow searching for neural correlates of subtypes of adolescent-onset substance dependence. We will recruit, complete extensive diagnostic interviews and image subjects while they play the AlAn's game. That game, which was designed for use in the MRI environment, has demonstrated a strong relationship with CU trait scores in our out-of-magnet pilot testing. PUBLIC HEALTH RELEVANCE: Substance use disorders and antisocial behavior are major public health problems, are linked to serious morbidity and high mortality and have a partial genetic etiology. Callous-unemotional traits are identifiable in childhood and adolescents, are relatively stable into young adulthood and predict future and persistent antisocial behavior and substance problems. The current study proposes a search for neurobiological correlates callous-unemotionality and subtypes of adolescent-onset substance dependence. Better understanding the biological etiology of these disorders may lead to better prevention or treatment approaches.